Bioactive lysolipids in cancer and angiogenesis

Abstract

While normal angiogenesis is critical for development and tissue growth, pathological angiogenesis is important for the growth and spread of cancers by supplying nutrients and oxygen as well as providing a conduit for distant metastasis. The interaction among extracellular matrix molecules, tumor cells, endothelial cells, fibroblasts, and immune cells is critical in pathological angiogenesis, in which various angiogenic growth factors, chemokines, and lipid mediators produced from these cells as well as hypoxic microenvironment promote angiogenesis by regulating expression and/or activity of various related genes. Sphingosine 1-phosphate and lysophosphatidic acid, bioactive lipid mediators which act via specific G protein-coupled receptors, play critical roles in angiogenesis. In addition, other lipid mediators including prostaglandin E, lipoxin, and resolvins are produced in a stimulus-dependent manner and have pro- or anti-angiogenic effects, presumably through their specific GPCRs. Dysregulated lipid mediator signaling pathways are observed in the contxt of some tumors. This review will focus on LPA and S1P, two bioactive lipid mediators in their regulation of angiogenesis and cell migration that are critical for tumor growth and spread.

Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+T cells

“…LPA signals through six GPCRs, termed LPAR1-6 or LPA1-6, showing both distinct and overlapping signaling activities (Yanagida et al, 2013;Yung et al, 2014). LPAR1-3 belong to the EDG family of GPCRs together with the sphingosine 1-phosphate (S1P) receptors, whereas the disparate LPAR4-6 members are related to the purinergic receptors (Hisano and Hla, 2019;Yanagida et al, 2013).…”

Targeting the Sphingolipid System as a Therapeutic Direction for Glioblastoma

“…Taken together, these data suggest that the modulation of ceramide and ceramide synthases may be a viable therapeutic target in GBM 5.4. Sphingosine 1-Phosphate-Mediated Cell Signaling S1P has roles in cell survival, migration and angiogenesis, and is known to play an important role in cancer [194][195][196][197][198].…”

Exosomes in chronic inflammatory skin diseases and skin tumors

“…Overall, melanoma‐derived exosomes induce a protumor macrophage activation phenotype . EMT is vital for the distant metastasis of cancers . The invasion and migration of primary melanocytes can be enhanced through an EMT‐resembling process induced by exosomes derived from melanoma cells …”

“…[59] EMT is vital for the distant metastasis of cancers. [60,61] The invasion and migration of primary melanocytes can be enhanced through an EMT-resembling process induced by exosomes derived from melanoma cells. [62] CD8+ T lymphocytes play a crucial role in adaptive immunity and can directly kill cancer cells.…”